PI: Dmitri O. Lapotko, Co-PI: Jason H. Hafner, Research Scientist: Ekaterina U. Lukianova-Hleb

• Plasmonic nanobubbles: laser pulse and plasmonic nanoparticle-generated transient event with tunable optical and mechanical properties.

• Physical and optical properties of plasmon nanoparticles at high temperatures and in multi-phase environment.

• Methods for imaging and characterization of plasmon nanoparticles.

• Heat transfer at nano-scale.

• Interaction of plasmonic nanobubbles with living cells and tissue.

• Zebrafish: optically transparent organism as a model for plasmonic nanomedicine

• Cell theranostics: dynamically tuned intracellular plasmonic nanobubbles combine diagnosis (through optical scattering), therapy (through mechanical, nonthermal and selective damage of target cells) and optical guidance of the therapy into one fast process.

• High-sensitive imaging and diagnosis of cells with plasmonic nanobubbles that may provide up to 102-3-fold increase in sensitivity compared to gold nanoparticles and 105-6 fold increase in sensitivity compared to fluorescent molecules.

• Targeted therapy with plasmonic nanobubbles: LANTCET (laser activated nano-thermolysis as cell elimination technology). Applicastions: treatment of leukemia and of superficial tumors.

• Controlled release and intracellular delivery of therapeutic and diagnostic agent into the cells.

• Methods for imaging plasmonic nanoparticles in living cells and in tissue.

• Micro-surgery with plasmonic nanobubbles: recanalization of occluded coronary arteries.

PUBLICATIONS

1. Lapotko D., Laser calorimetry technique in cytometry. Anal. Cell. Pathol. 1992, 9, 186-187.
The first disclosure of the concept of photothermal cytometry for living cells: using the laser-induced photothermal effects (transient thermal field due to optical absorption by endogenous chromophores) for optical sensing of living cells without any chemicals and probes and with high sensitivity.

2. Lapotko D., Kuchinsky G., Potapnev M., Pechkovsky D., Photothermal image cytometry of human neutrophils. Cytometry 1996, 24, 198-203.
We reported the first experimentally obtained photothermal images of individual intact living cells and the photothermal microscope for such imaging. Laser pulse was absorbed by cellular chromophores (hem-proteins) and the released heat was mapped as the photothermal image that correlated to diagnoses. The method was patented (Lapotko D.O., Zharov V.P., Method and device for photothermal examination of microinhomogeneities, US patent 7230708, 2007).

3. Lapotko D., Kuchinsky G., Antonishina E., Scoromnik E., Laser viability method for red blood cell state monitoring. Proc. SPIE. Optical and Imaging Techniques for Biomonitoring 1996, 2628, 340-348.
Disclosure of the photothermal method for quantitative and high sensitivity analysis of the physiological and functional state of individual living cells by using laser-induced transient thermal field as a non-specific load and by monitoring optically the cell response to the above load (referred as Laser Viability Test).The method has allowed to monitor the activity of the electron transport chain in individual intact cells (hepatocytes, see also Lapotko D., Romanovskaya T., Gordiyko E., Photothermal monitoring of redox state of respiratory chain in single live cells. Photochem. Photobiol. 2002, 75, 519-526).

4. Zharov V., Lapotko D., Photothermal sensing of nanoscale targets. Rev. Sci. Instr. 2003, 74, 785-788.
Individual gold nanoparticles were imaged with transient vapour bubbles generated around them with a short laser pulse. Later this method was applied for imaging gold nanoparticles and their internalization and clusterization in living cells (Lapotko D., Lukianova-Hleb E., Oraevsky A., Clusterization of nanoparticles during their interaction with living cells. Nanomedicine 2007, 2, 241–253).

5. Lapotko D., Lukianova E., Shnip A., Zheltov G., Potapnev M., Oraevsky A., Savitskiy V., Klimovich A., Photothermal microscopy and laser ablation of leukemia cells targeted with gold nanoparticles. Proc. SPIE 2005, 5697, 82-89.
Disclosure of the concept and of the experimental proof for cell nano-therapy that was based on gold nanoparticle clusterization in target cells and on the laser-activated transient vapor bubble generation for selective killing of the target cells. This concept has been developed as Laser-Activated Nano-Thermolysis as Cell Elimination Technology (LANTCET), was tested for cleaning human bone marrow of residual leukemia cells, has demonstrated single cell selectivity and was later published and patented (Lapotko D., Lukianova E., Potapnev M., Aleinikova O., Oraevsky A., Method of laser activated nanothermolysis for elimination of tumor cells. Cancer Letters 2006, 239, 36-45; Lapotko D.O., Oraevsky A. US patent application, WO/2006/078987 2006).

6. Hleb E., Lapotko D., Influence of transient environmental photothermal effects on optical scattering by gold nanoparticles. Nano Letters 2009, 9, 2160-2166.
We have reported new optical properties of plasmonic (gold) nanoparticles (with attenuation or amplification of optical scattering by several orders of magnitude) when plasmonic interaction involved vapor nanobubbles. Thus the nanoparticle-generated vapor nanobubbles were demonstrated as optical probes that provide high sensitivity and contrast.

7. Lapotko D., Optical excitation and detection of vapor bubbles around plasmonic nanoparticles, Optics Express 2009, 17, 2538-2556.
We have reported the mechanisms of optical generation and detection of the transient vapor nanobubbles around gold nanoparticles. These nanoscale mechanisms were found to be different from those for the vapor bubbles generated around micro- and macro-absorbers. This allows promising biomedical applications of the nanobubbles

8. Lapotko D. Plasmonic nanoparticle-generated photothermal bubbles and their biomedical applications. Nanomedicine 2009, 7, 813-845.
A review of science and application of plasmonic nanobubbles

9. E .Y .Lukianova-Hleb, E. Y. Hanna, J. H. Hafner, D. O. Lapotko, Tunable plasmonic nanobubbles for cell theranostics. Nanotechnology 2010, 21, 085102.
Disclosure of the concept and of the experimental proof for cell theranostics with plasmonic nanobubbles. Gold nanoparticle-generated vapor nanobubbles were generated in cancer cells with a single laser pulse as (1) non-invasive optical scattering probes and (by increasing the fluence of laser pulse) as a mechanical selective therapeutic agent (that disrupted and killed the cell), which optical parameters allowed us to guid the therapeutic action in a real time.

Collaborators
A.V. Lykov Heat and Mass Transfer Institute (Minsk, Belarus)
MD Anderson Cancer Center (Houston, TX)